Kansas City—Using replacement therapy to normalize testosterone levels appears to have a positive effect on the risk of cardiovascular (CV) events for older men, according to a study of U.S. veterans.

The report, published in the European Heart Journal, examined the effect of testosterone replacement therapy (TRT) on cardiovascular outcomes by comparing incidences of heart attack, stroke, and all-cause mortality among different sub-populations of treated and untreated patients. For the study, researchers from the Kansas City Veterans Affairs Medical Center used the largest cohort of patients and the longest follow-up for TRT to date.

Of the 83,010 male veterans, all without history of myocardial infarction (MI) or stroke, for which data was reviewed between December 1999 and May 2014, only 63% of patients achieved normal testosterone levels after TRT use. That group was found to have had significantly fewer deaths and CV events than those whose testosterone levels were not normalized.

“With such widespread and ever increasing use of TRT, there has been growing concern regarding its effect on mortality, as well as conflicting results,” explained co-author Rajat S. Barua, MD PhD. “Our aim was to address the knowledge gap.”

For the study, the veterans were divided into three groups: the first receiving TRT and achieving normal levels; the second receiving TRT but failing to achieve normal levels, and a third receiving no replacement therapy.

According to the results, the greatest difference was between the first and the last group—the men who were successfully treated with TRT were 56% less likely to die during the follow-up period, 24% less likely to suffer a heart attack, and 36% less likely to have a stroke than those who received no treatment at all.

The differences between the patients whose TRT normalized testosterone levels compared to those who used TRT without achieving normalization were similar but less significant. In fact, the second and third groups showed little difference when it came to risk for CV events, although those who received TRT had a slight survival advantage, according to the study.

“In this study of men, without previous history MI or stroke, with low testosterone levels, normalization of testosterone levels using TRT is associated with lower mortality, fewer MIs, and strokes,” Barua said in a journal press release. “This is the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the testosterone levels.”

The researchers also caution against “off-label” use, emphasizing, “None of the FDA-approved testosterone products are approved for use in men with low testosterone levels who lack an associated medical condition.”